"Although several immunological reagents have been developed (ex: tumor infiltrating lymphocytes, antigen specific tumor vaccines etc.) during the last few years which can recognize and kill melanoma cells and have the potential of curing melanoma patients, most patients are resistant to this form of therapy. This resistance is probably dependent upon a complexity of variables affecting the balance between activation of the immune system and growth of tumor cells in vivo and our limited understanding of them. My work is focused on analyzing variables potentially affecting this balance. During the last year we have further addressed several issues related to this topic, specifically: 1. The significance of the genetic polymorphism of HLA in modulating the cellular immune response toward melanoma. Melanoma patients are genetically variable according to their ethnic ancestry and this variability determines their immunologic reactivity. 2. The significance of individual variability in natural and vaccine induced immunocompetence against MAA. Evidence for in vivo priming of patients T cells against melanoma antigens and the effectiveness of peptide based vaccination protocols was characterized. 3. We described several mechanisms of tumor escape including aberrations in HLA expression as well as variability in expression of melanoma associated antigens. 4. The significance of quality and intensity of epitope directed T cell sensitization was analyzed and definition of stringent allele/epitope requirements for melanoma antigen immunodominance was defined. 5. T cell cloning and TCR utilization technology was developed to follow T cell expansion and localization during and after patient vaccination. Most recently two new technologies were added including HLA tetramer based analysis of CTL precursor frequency and analysis of gene expression by real time quantitative RT-PCR"